Liu Li, Li Yi-Ning, Zhang Aimin, Yin Yue, Yue Zhihong, Pei Lin, Xia Chang-Sheng, Wang Dong, Jia Mei, Wang Hui, Cao Lin-Lin
Department of Clinical Laboratory, Peking University People's Hospital, Beijing 100044, China; Department of Clinical Laboratory, Beihua University Affiliated Hospital, Jilin 132011, China.
Department of Clinical Laboratory, Peking University People's Hospital, Beijing 100044, China.
Clin Chim Acta. 2024 Jul 15;561:119814. doi: 10.1016/j.cca.2024.119814. Epub 2024 Jun 13.
Hepatocellular cancer (HCC) is one of the most harmful tumors to human health. Currently, there is still a lack of highly sensitive and specific HCC biomarkers in clinical practice. In this study, we aimed to explore the diagnostic performance of prostaglandin A2 (PGA2) for the early detection of HCC.
Untargeted metabolomic analyses on normal control (NC) and HCC participants in the discovery cohort were performed, and PGA2 was identified to be dysregulated in HCC. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detecting serum PGA2 was established and applied to validate the dysregulation of PGA2 in another independent validation cohort. Receiver operating characteristic (ROC), decision curve analysis (DCA) and some other statistical analyses were performed to evaluate the diagnostic performance of PGA2 for HCC.
At first, PGA2 was found to be dysregulated in HCC in untargeted metabolomic analyses. Then a precise quantitative LC-MS/MS method for PGA2 has been established and has passed rigorous method validation. Targeted PGA2 analyses confirmed that serum PGA2 was decreased in HCC compared to normal-risk NC and high-risk cirrhosis group. Subsequently, PGA2 was identified as a novel biomarker for the diagnosis of HCC, with an area under the ROC curve (AUC) of 0.911 for differentiating HCC from the combined NC + cirrhosis groups. In addition, PGA2 exhibited high performance for differentiating small-size (AUC = 0.924), early-stage (AUC = 0.917) and AFP (-) HCC (AUC = 0.909) from the control groups. The combination of PGA2 and AFP might be useful in the surveillance of risk population for HCC and early diagnosis of HCC.
This study establishes that PGA2 might be a novel diagnostic biomarker for HCC.
肝细胞癌（HCC）是对人类健康危害最大的肿瘤之一。目前，临床实践中仍缺乏高灵敏度和特异性的HCC生物标志物。在本研究中，我们旨在探索前列腺素A2（PGA2）在HCC早期检测中的诊断性能。
对发现队列中的正常对照（NC）和HCC参与者进行非靶向代谢组学分析，发现PGA2在HCC中表达失调。建立了一种用于检测血清PGA2的液相色谱-串联质谱（LC-MS/MS）方法，并应用于另一个独立验证队列中验证PGA2的失调情况。进行了受试者工作特征（ROC）、决策曲线分析（DCA）和其他一些统计分析，以评估PGA2对HCC的诊断性能。
首先，在非靶向代谢组学分析中发现PGA2在HCC中表达失调。然后建立了一种精确的PGA2定量LC-MS/MS方法，并通过了严格的方法验证。靶向PGA2分析证实，与正常风险NC组和高风险肝硬化组相比，HCC患者血清PGA2降低。随后，PGA2被确定为诊断HCC的新型生物标志物，用于区分HCC与合并的NC + 肝硬化组的ROC曲线下面积（AUC）为0.911。此外，PGA2在区分小尺寸（AUC = 0.924）、早期（AUC = 0.917）和AFP（-）HCC（AUC = 0.909）与对照组方面表现出高性能。PGA2和AFP的联合检测可能有助于HCC风险人群的监测和HCC的早期诊断。
本研究表明PGA2可能是一种新型的HCC诊断生物标志物。
